KDELR2 promotes bone marrow mesenchymal stem cell osteogenic differentiation via GSK3β/β-catenin signaling pathway

doi:10.1007/s00441-024-03884-9

. 2024 May;396(2):269-281.

doi: 10.1007/s00441-024-03884-9. Epub 2024 Mar 12.

KDELR2 promotes bone marrow mesenchymal stem cell osteogenic differentiation via GSK3β/β-catenin signaling pathway

Xiaoyong Wu^#^{1

2

3

4}, Weijun Zhang^#^{1

2

3

4}, Long Long^#^{1

2

3

4

5}, Yibo Wang^{6

7}, Hongyu Chen^{1

2

3

4}, Kanbin Wang^{1

2

3

4}, Zhongxiang Wang^{1

2

3

4}, Jinwu Bai^{1

2

3

4}, Deting Xue^{8

9

10

11}, Zhijun Pan^{12

13

14

15}

Affiliations

¹ Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou 310009, China.
² Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China.
³ Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzou City, Zhejiang Province, PR China.
⁴ Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou City, PR China.
⁵ Linping Hospital of Integrated Chinese and Western Medicine, No.60,Baojian Road, Hangzhou, 310009, China.
⁶ Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
⁷ Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
⁸ Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou 310009, China. blueskine@zju.edu.cn.
⁹ Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China. blueskine@zju.edu.cn.
¹⁰ Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzou City, Zhejiang Province, PR China. blueskine@zju.edu.cn.
¹¹ Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou City, PR China. blueskine@zju.edu.cn.
¹² Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou 310009, China. zrpzj@zju.edu.cn.
¹³ Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China. zrpzj@zju.edu.cn.
¹⁴ Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzou City, Zhejiang Province, PR China. zrpzj@zju.edu.cn.
¹⁵ Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou City, PR China. zrpzj@zju.edu.cn.

^# Contributed equally.

PMID: 38470494
DOI: 10.1007/s00441-024-03884-9

KDELR2 promotes bone marrow mesenchymal stem cell osteogenic differentiation via GSK3β/β-catenin signaling pathway

Xiaoyong Wu et al. Cell Tissue Res. 2024 May.

. 2024 May;396(2):269-281.

doi: 10.1007/s00441-024-03884-9. Epub 2024 Mar 12.

Authors

Affiliations

¹ Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou 310009, China.
² Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China.
³ Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzou City, Zhejiang Province, PR China.
⁴ Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou City, PR China.
⁵ Linping Hospital of Integrated Chinese and Western Medicine, No.60,Baojian Road, Hangzhou, 310009, China.
⁶ Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
⁷ Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
⁸ Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou 310009, China. blueskine@zju.edu.cn.
⁹ Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China. blueskine@zju.edu.cn.
¹⁰ Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzou City, Zhejiang Province, PR China. blueskine@zju.edu.cn.
¹¹ Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou City, PR China. blueskine@zju.edu.cn.
¹² Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou 310009, China. zrpzj@zju.edu.cn.
¹³ Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China. zrpzj@zju.edu.cn.
¹⁴ Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzou City, Zhejiang Province, PR China. zrpzj@zju.edu.cn.
¹⁵ Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou City, PR China. zrpzj@zju.edu.cn.

^# Contributed equally.

PMID: 38470494
DOI: 10.1007/s00441-024-03884-9

Abstract

Nonunion is a challenging complication of fractures for the surgeon. Recently the Lys-Asp-Glu-Leu (KDEL) endoplasmic reticulum protein retention receptor 2 (KDELR2) has been found that involved in osteogenesis imperfecta. However, the exact mechanism is still unclear. In this study, we used lentivirus infection and mouse fracture model to investigate the role of KDELR2 in osteogenesis. Our results showed that KDELR2 knockdown inhibited the osteogenic differentiation of mBMSCs, whereas KDELR2 overexpression had the opposite effect. Furthermore, the levels of active-β-catenin and phospho-GSK3β (Ser9) were upregulated by KDELR2 overexpression and downregulated by KDELR2 knockdown. In the fracture model, mBMSCs overexpressing KDELR2 promoted healing. In conclusion, KDELR2 promotes the osteogenesis of mBMSCs by regulating the GSK3β/β-catenin signaling pathway.

Keywords: GSK3β/β-catenin; KDELR2; Osteogenesis; mBMSCs.

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References

1. Bajaj R, Kundu ST, Grzeskowiak CL et al (2020) IMPAD1 and KDELR2 drive invasion and metastasis by enhancing Golgi-mediated secretion. Oncogene 39:5979–5994. https://doi.org/10.1038/s41388-020-01410-z - DOI - PubMed - PMC
1. Beaver R, Brinker MR, Barrack RL (1997) An analysis of the actual cost of tibial nonunions. J La State Med Soc Off Organ La State Med Soc 149(6):200–206
1. Beurel E, Grieco SF, Jope RS (2015) Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases. Pharmacol Ther 148:114–131. https://doi.org/10.1016/j.pharmthera.2014.11.016 - DOI - PubMed
1. Braga Frade B, da Cunha D, Muller L, Bonfim DC (2022) Establishing a Diaphyseal Femur Fracture Model in Mice. J vis Exp JoVE. https://doi.org/10.3791/64766 - DOI - PubMed
1. Bruder SP, Kurth AA, Shea M et al (1998) Bone regeneration by implantation of purified, culture-expanded human mesenchymal stem cells. J Orthop Res off Publ Orthop Res Soc 16:155–162. https://doi.org/10.1002/jor.1100160202 - DOI

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[1] Bajaj R, Kundu ST, Grzeskowiak CL et al (2020) IMPAD1 and KDELR2 drive invasion and metastasis by enhancing Golgi-mediated secretion. Oncogene 39:5979–5994. https://doi.org/10.1038/s41388-020-01410-z - DOI - PubMed - PMC

[2] Bajaj R, Kundu ST, Grzeskowiak CL et al (2020) IMPAD1 and KDELR2 drive invasion and metastasis by enhancing Golgi-mediated secretion. Oncogene 39:5979–5994. https://doi.org/10.1038/s41388-020-01410-z - DOI - PubMed - PMC

[3] Beaver R, Brinker MR, Barrack RL (1997) An analysis of the actual cost of tibial nonunions. J La State Med Soc Off Organ La State Med Soc 149(6):200–206

[4] Beaver R, Brinker MR, Barrack RL (1997) An analysis of the actual cost of tibial nonunions. J La State Med Soc Off Organ La State Med Soc 149(6):200–206

[5] Beurel E, Grieco SF, Jope RS (2015) Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases. Pharmacol Ther 148:114–131. https://doi.org/10.1016/j.pharmthera.2014.11.016 - DOI - PubMed

[6] Beurel E, Grieco SF, Jope RS (2015) Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases. Pharmacol Ther 148:114–131. https://doi.org/10.1016/j.pharmthera.2014.11.016 - DOI - PubMed

[7] Braga Frade B, da Cunha D, Muller L, Bonfim DC (2022) Establishing a Diaphyseal Femur Fracture Model in Mice. J vis Exp JoVE. https://doi.org/10.3791/64766 - DOI - PubMed

[8] Braga Frade B, da Cunha D, Muller L, Bonfim DC (2022) Establishing a Diaphyseal Femur Fracture Model in Mice. J vis Exp JoVE. https://doi.org/10.3791/64766 - DOI - PubMed

[9] Bruder SP, Kurth AA, Shea M et al (1998) Bone regeneration by implantation of purified, culture-expanded human mesenchymal stem cells. J Orthop Res off Publ Orthop Res Soc 16:155–162. https://doi.org/10.1002/jor.1100160202 - DOI

[10] Bruder SP, Kurth AA, Shea M et al (1998) Bone regeneration by implantation of purified, culture-expanded human mesenchymal stem cells. J Orthop Res off Publ Orthop Res Soc 16:155–162. https://doi.org/10.1002/jor.1100160202 - DOI

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KDELR2 promotes bone marrow mesenchymal stem cell osteogenic differentiation via GSK3β/β-catenin signaling pathway

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KDELR2 promotes bone marrow mesenchymal stem cell osteogenic differentiation via GSK3β/β-catenin signaling pathway

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